Ophthalmological Disease Product Pipeline

About XLRP and Choroideremia

XLRP is a rare inherited X-linked recessive genetic disorder that causes progressive vision loss and blindness in boys and young men. There are currently no approved therapies for XLRP. Seventy percent of cases are caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. The estimated worldwide prevalence of XLRP due to RPGR variants is approximately one in 25,600 people, which represents approximately 24,000 patients in the United States and EU-5.

Choroideremia is a monogenic blinding disease, affecting approximately 13,000 patients in the United States and EU-5. No products are approved currently for the treatment of this disease. This X-linked, progressive degenerative disease of the retina and choroid is caused exclusively by mutations in the CHM gene that encodes for the REP1 protein.

Conventional AAV gene therapy approaches under development for XLRP, Choroideremia and other rare retinal diseases require delivery by subretinal injections.

About Wet Age-related Macular Degeneration (Wet AMD) and Diabetic Retinopathy

Wet AMD is a type of macular degeneration where abnormal blood vessels, (choroidal neovascularization or CNV) grow into the macula, the central area of the retina. As a consequence, CNV causes retina swelling and edema, and bleeding can occur and cause visual distortion and reduced acuity. The proliferation of abnormal blood vessels in the retina is stimulated by VEGF. This process distorts and can potentially destroy central vision and may progress to blindness without treatment. There are on average 200,000 new incidences of wet AMD per year in the United States alone.

Diabetic eye disease, primarily diabetic retinopathy (DR), is a leading cause of vision loss and blindness in working-age adults and occurs due to the development of diabetic macular edema (DME; swelling, edema and hemorrhage in the central vision) and complications arising from proliferative diabetic retinopathy (PDR; retinal neovascularization causing bleeding and retinal detachment). The prevalence of diabetic retinopathy is high, affecting almost one-third of adults over 40 years of age with diabetes. In the United States approximately 4.2 million adults have DR and 655,000 have vision-threatening DR.

adRP is a rare inherited autosomal dominant genetic disorder that occurs in both sexes and causes progressive vision loss and blindness. adRP is characterized by dysfunction and degeneration of photoreceptors in the retina. Symptoms of adRP are initially characterized by night blindness, followed by loss of peripheral visual field, decreasing visual acuity and eventually blindness. There are currently no approved therapies for adRP. Approximately 35% of adRP cases are caused by mutations in the rhodopsin (RHO) gene. The estimated worldwide prevalence of adRP due to RHO variants is approximately one in 52,000 people, which represents approximately 11,600 patients in the United States and EU-5.

4DMT Pipeline Products: 4D-125, 4D-110, 4D-150 & 4D-135

Our ophthalmology product candidates utilize our proprietary intravitreal vector, R100.

4D-125 is enrolling patients in an ongoing Phase 1/2 dose-escalation clinical trial in patients with XLRP related to mutations in the RPGR gene. The primary endpoint of this trial is to determine the safety and maximum-tolerated dose. Secondary endpoints include assessments of biologic activity, including both visual field function and anatomical endpoints. 4DMT currently holds the worldwide commercialization rights for 4D-125 and Roche holds an exclusive option to in-license the product prior to pivotal trial initiation.

4D-110, is enrolling patients in an ongoing Phase 1 dose-escalation clinical trial in patients with choroideremia related to mutations in the CHM gene. The primary endpoint of this trial is to determine the safety and maximum-tolerated dose. Secondary endpoints include assessments of biologic activity, including visual acuity, visual field function and anatomical endpoints. Roche in-licensed worldwide rights to 4D-110.

We also have two wholly owned preclinical product candidates. We are developing 4D-150 for the treatment of wet AMD and diabetic retinopathy and 4D-135 for the treatment of adRP.